U.S. Pat. No. 1,970,396 to R. P. Scherer describes an early method and machine for producing soft gelatin capsules in an automated process. The process involves the formation of two gelatin sheets or films through the use of a gravity fed spreader box, cooling the liquid gelatin on two separate webs, then lubricating and guiding the two sheets into communication with each other between two co-acting dies while simultaneously dispensing the proper amount of medicine or other filling material between the sheets in registration with half cavities in the outer surface of the dies.
U.S. Pat. No. 4,817,367 to Ishikawa et al. introduced some improvements to the basic machine to aid in the set up, operation and quality of the capsules produced, however, a gravity fed spreader box was still used to form the gelatin ribbons or sheets.
U.S. Pat. No. 5,761,886 to Parkhideh discloses an apparatus for forming capsules that provides rotary dies that are independently moveable and the ability to vary the speed of the dies during the formation of a single capsule. The Parkhideh device also utilizes independently controlled casting drums to reduce “set-up” time and provide better quality control. Even though Parkhideh discloses a very sophisticated encapsulation machine, it still utilizes a gravity feed spreader box for formation of the encapsulating ribbon. Other patents relating to encapsulation techniques which disclose the use of spreader boxes to create the film or ribbon on a casting drum include U.S. Pat. No. 5,246,638 to Ratko et al.; U.S. Pat. No. 5,735,105 to Stroud et al.; U.S. Pat. No. 2,774,988 to Stirn et al.; U.S. Pat. No. 6,022,499 to Schurig et al.; and U.S. Pat. No. 2,288,327 to Scherer.
One interesting reference is U.S. Pat. No. 4,028,024 to Moreland. It discloses a process and apparatus that prepares a gelatin encased medicament. The gelatin and the active are co-extruded as a column. This column is then pinched off by a pair of rotating wheels, each having half cavities therein to form capsules.
These previously utilized machines have many structural and operational shortcomings. Many of the shortcomings relate to the “set-up” of the machine. For example, the die to die timing, pump timing, ribbon formation and wedge adjustments are all important in protecting the equipment and providing a quality product. One aspect of the present invention resides in the use of a melt-on-demand extrusion technology and/or a valved wedge to decrease set-up time, reduce costs and improve product quality. The apparatus and process of the present invention allows for the use of encapsulating materials that were previously unusable on a standard rotary die encapsulation machine due to high viscosities or processing temperatures.
A general discussion of the basic technology, apparatuses and processes relating to the preparation of soft capsules is described in The Theory and Practice of Industrial Pharmacy (Lachman, Liberman and Kanig) 3rd edition, published by Lee & Febiger.
Conventional technology for the manufacture of soft capsules using the rotary die process typically utilizes a spreader box metering system to cast the films or sheets onto a chilled surface, i.e., the casting drum. The present invention differs from conventional technology by the method of producing the sheets, ribbons or films. In the inventive process, extrusion dies are used as an alternative to spreader boxes. Further, the film-forming composition is not kept molten but rather is allowed to solidify and only the amount needed is melted just prior to its placement on the casting drum. In addition, the novel valved wedge according to the invention provides economical set-up of the encapsulation machine.
The conventional process of producing gelatin films comprises mixing gelatin, plasticizers and water, and heating the mixture while stirring under vacuum. The gelatin and excipients are heated under vacuum with mixing until a molten homogenous mixture is produced that is referred to as a gelatin melt. This occurs at approximately 45–65° C. The molten system is drained into heated tanks that maintain the gelatin in a molten state during staging and casting of the films. Staging can be as long as two to three days. Before encapsulation, other additives such as colorants, preservatives, sweeteners, flavors, texture modifiers and the like may be blended into the gelatin melt.
During the prior art encapsulation process, the molten gelatin melt is transferred to the metering devices (spreader boxes) which are used to cast ribbons with a required thickness onto the casting drum. Commonly, the metering device consists of a heated reservoir that uses a gate box (a heated chamber or box with the rear portion fitted with a variable height slot) wherein the material flows via gravity through the slot onto the rotating casting drum. Film thickness is determined primarily by the height of the slot. Item 8 in Parkhideh, U.S. Pat. No. 5,761,886, is a spreader box. A second type of metering device meters the gelatin onto the rotating casting drum using doctor blades. A rotating cylinder mounted adjacent to the doctor blade assists with the flow of the gelatin. Ribbon thickness is determined by a) the gap between the doctor blade and the casting drum surface; and b) the speed of the spreader box cylinder. The cast ribbon solidifies onto the rotating casting drum after leaving the spreader box and this can take up to 10 to 15 seconds to achieve. The typical spreader boxes are vented to the atmosphere and are not capable or designed to support pressure to facilitate the casting process.
U.S. Pat. No. 2,775,257 to Stirn et al. discusses some of the shortcomings associated with the prior art gelatin film casting machines. This reference describes the use of casting hoppers where it has been found that the surface of the gelatin composition exposed to the air lost moisture by evaporation and formed a comparatively hard, inflexible scum or skin. Additionally, changes in the gelatin composition introduced by the evaporation of moisture from the surface caused undesirable variations in the film. Stirn et al. found that by placing a layer of an inert liquid, such as mineral oil, on the surface of the gelatin composition, evaporation from the hoppers was prevented. This reference also provides a fairly good description of the use of a casting hopper or spreader box to form the ribbons.
In the prior art process, transfer of molten gelatin from the holding tank to the metering device (or spreader box) is achieved in one of two ways. A common method is to suspend or mount the tank of molten gelatin above the encapsulation machine and allow the molten material to gravity feed through heated tubes into the reservoir of the metering device. Another transfer method conventionally used is to pump the molten gelatin via heated tubes from floor mounted gelatin staging tanks using either a peristaltic or lobe pump system. One shortcoming of the pump feed system is that the pump casing/components and in-line connections must be maintained above the melting point of the film-forming composition. If there are cold areas within the path, the material will freeze and prevent flow. In addition, both gravity and pump systems require a method of controlling flow to prevent overfilling of the spreader boxes.
The conventional process also relies on maintaining the gelatin melt in a molten state from initial manufacture to just before encapsulation. Tanks used to feed the encapsulation machine require the entire tank to be maintained above the melt temperature of the film-forming composition. Prolonged maintenance of gelatin or other film-forming compositions in a molten state leads to degradation of the polymer, rendering the gelatin after prolonged staging, ineffective at fabricating capsules. Gelatin melts can be staged typically no longer than 96 hours before unacceptable degradation occurs.
Gelatin can be cooled and allowed to solidify within the staging tanks to prevent degradation if prolonged staging is required. However, the major drawback is that the entire tank contents have to be remelted. This requires 8 to 15 hours of gently heating the material to raise the temperature of the gelatin mass to the required 60° C. Rapid heating of the system leads to localized heating, which can cause degradation and charring of the composition. Therefore, when stopping the encapsulation machine, a decision has to be made to: 1) continue to heat the gelatin which subjects it to degradation; or 2) allow it to solidify. The solidification subsequently requires the remelting which is very time consuming and expensive. Often, the result of stopping the encapsulation machine is that the melt is discarded which represents a significant waste of resources. Thermal degradation is often exacerbated by the addition of additives and can significantly shorten the available staging time.
Another drawback of the conventional process and apparatus is that it requires relatively low viscosities of the film-forming compositions. Spreader boxes rely on viscosities sufficiently low to enable the material to flow from the exit slot. The use of doctor blades and a rotating cylinder will enable slightly higher viscosity materials to be cast into films, but there is still a limit of about 20,000 to 25,000 cps on these metering systems. The conventional equipment and methodology therefore precludes the use of high viscosity film-forming compositions. Most alternative polymer compositions for forming films have viscosities significantly higher than that of gelatin.
An example of a film-forming composition that is not gelatin based is disclosed in International Application No. PCT/US00/18420, entitled: FILM-FORMING COMPOSITIONS COMPRISING MODIFIED STARCHES AND IOTA-CARRAGEENAN AND METHODS FOR MANUFACTURING SOFT CAPSULES USING SAME. In general, this application discloses an edible, soft capsule which comprises a soft, dry shell which comprises i) about 12–24 weight % iota-carrageenan; ii) about 30–60 weight % modified starch; iii) about 10–60 weight % plasticizer; and iv) about 1–4 weight % sodium phosphate dibasic buffer system. The viscosity of these compositions can range from 10,000 to above 30,000 cps and have proven to be difficult to utilize on the conventional encapsulation machinery. One aspect of the present invention resides in the discovery that these gelatin free compositions can be effectively utilized in the encapsulation system disclosed herein.
A further limitation of conventional equipment and methodologies is that it is extremely difficult to use a spreader box to form laminated ribbons. Laminated ribbons are ribbons that are cast one on top of the other. Laminated ribbons are sometimes desirable to modify the functional properties of the film, i.e., modifying the drying characteristics or retaining fill materials that are incompatible with standard encapsulation polymers. Through the use of the inventive melt-on-demand extrusion apparatus of the present invention, laminated ribbons are easily produced.